Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases

Our plain-English summary of Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases, by Y. Nishimura, Y. Miura, M. Maeda, et al (International Journal of Immunopathology and Pharmacology, 2006).

The study

• Authors: Y. Nishimura, Y. Miura, M. Maeda, H. Hayashi, M. Dong, H. Katsuyama, M. Tomita, F. Hyodoh, M. Kusaka, A. Uesaka, K. Kuribayashi, K. Fukuoka, T. Nakano, T. Kashimoto, T. Osuki
• Journal: International Journal of Immunopathology and Pharmacology
• Published: 2006;19(4):795-805
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To explore the effects of asbestos and silica on the human immune system, an experimental model of low-dose and long-term exposure was established using a human HTLV-1-immortalized polyclonal T cell line, MT-2 (MT-2Org). MT-2 cells were continuously exposed to asbestos at a concentration (10 microg/ml) which does not induce complete cell death during short-term exposure. After acquiring resistance to CB-induced apoptosis (designated MT-2Rst), an immunological comparison was made between the MT-2Org and MT-2Rst lines in terms of T cell receptor-Vbeta (TcR-Vbeta) expression. MT-2Rst cells showed excess expression of various TcR-Vbeta, although TcR-Vbeta-overpresenting cells were characterized as undergoing apoptosis due to first contact with CB. Patients with asbestos-related diseases (ARD), such as asbestosis and malignant mesothelioma, were compared with silicosis (SIL) patients as a disease control and with healthy donors (HD). SIL and ARD not only differed in their causative materials, silica and asbestos as mineral silicates, but also in terms of complications; autoimmune disorders in SIL and tumors in ARD. ARD patients showed a restricted overpresentation of TcR-Vbeta without clonal expansion, whereas SIL patients revealed significant overpresentation of TcR-Vbeta 7.2. These experimental and clinical analyses indicate the superantigenic and dysregulation of autoimmunity-inducing effects of asbestos and silica, respectively.

In plain English

This report combined a cell-culture experiment with a clinical comparison of T cell receptor Vbeta (TcR-Vbeta) use. The authors continuously exposed the HTLV-1-immortalized human polyclonal T cell line MT-2 to 10 microg/ml chrysotile-B (UICC standard) for more than eight months, producing a subline resistant to chrysotile-B-induced apoptosis (MT-2Rst), and compared it with the original line (MT-2Org). MT-2Rst showed excess expression of TcR-Vbeta 1, 5.2, 9, 13.1, 13.2, 14, 18, 21.3 and 22, while MT-2Org resembled healthy donor blood cells. Sorted TcR-Vbeta 21.3-positive cells showed DNA synthesis almost equal to medium-only control and nuclear condensation and splitting. Blood CD3+ cells were also examined from six healthy donors, 13 silicosis, nine asbestosis and twelve malignant mesothelioma patients in Japan. Most asbestosis and mesothelioma patients had one or more TcR-Vbeta above the healthy-donor mean plus 2 SD, which the authors described as overrepresentation but without evidence of clonal expansion, adding that clonal expansion should be confirmed by genomic rearrangement; TcR-Vbeta 7.2 was significantly higher in silicosis than in the other three groups. The authors interpreted these as superantigenic (asbestos) and autoimmunity-dysregulating (silica) effects.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiment with a human T cell line exposed long-term to chrysotile, combined with a cross-sectional comparison of blood T cell receptor Vbeta expression in patient and healthy donor groups
• Who was studied: The MT-2 cell line (MT-2Org and the resistant subline MT-2Rst), and peripheral blood from six healthy donors, 13 silicosis patients, nine asbestosis patients and twelve malignant mesothelioma patients, recruited in Japan (Kawasaki Medical School, Okayama Rosai Hospital, Hyogo College of Medicine, Kusaka Hospital)
• Exposure: In vitro: continuous exposure of MT-2 cells to 10 microg/ml UICC standard chrysotile-B for more than eight months (and short-term culture with 0, 5, 10, 25 and 50 microg/ml). In patients: occupational silica exposure (silicosis) or asbestos exposure (asbestosis, malignant mesothelioma)
• Main results:
  • MT-2Rst cells excessively expressed TcR-Vbeta 1, 5.2, 9, 13.1, 13.2, 14, 18, 21.3 and 22, while the overall pattern of MT-2Org resembled that of healthy donor blood cells
  • Sorted TcR-Vbeta 21.3-positive MT-2Rst cells showed DNA synthesis almost equal to the medium-only control, whereas the negative fraction showed extensive synthesis
  • TcR-Vbeta 21.3-positive MT-2Rst cells showed nuclear condensation and splitting, taken by the authors as morphological indications of apoptosis; negative cells looked vivid
  • On re-exposure to chrysotile-B, MT-2Org showed a marked increase in TcR-Vbeta 21.3-positive cells compared with its original status, while the TcR-Vbeta 21.3-positive population in MT-2Rst was not much increased
  • In most asbestosis and mesothelioma patients, one or more TcR-Vbeta exceeded the healthy donor mean plus 2 SD; the text states six of nine (66.7%) MM patients and six of twelve (50%) ASB patients exceeded by more than 3%, to a maximum of 26.89% (these group sizes appear transposed relative to the Methods)
  • The authors described the asbestosis and mesothelioma patients as having a restricted TcR repertoire with Vbeta family overrepresentation but without evidence of clonal expansion
  • TcR-Vbeta 7.2 expression was significantly higher in silicosis patients than in healthy donors, asbestosis and mesothelioma patients; no other significant difference was found between groups
• The authors' conclusion: The authors concluded that asbestos-related disease patients showed a restricted TcR repertoire with Vbeta family overrepresentation but without evidence of clonal expansion, suggesting superantigen-driven T cell expansion, while silicosis patients showed overrepresentation with clonal expansion suggesting stimulation by specific antigens including self-antigens; overall they read the findings as superantigenic effects of asbestos and autoimmunity-inducing dysregulation by silica
• Limitations the authors state:
  • The authors state it remains unclear whether asbestos acts on T cells as a superantigen and causes a subsequent decline of tumour immunity
  • The authors note that clonal expansion should be confirmed by genomic rearrangement analysis
  • The silicosis subjects studied showed no signs or symptoms of autoimmune disturbance

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Apoptosis, Short-Term Exposure, Malignant Mesothelioma, Silicosis, Silicate.

Related studies

• Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells — Y. Miura, Y. Nishimura, et al. (2006)
• Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B — Z. Ma, T. Otsuki, et al. (1999)
• Involvement of the ICE family of proteases in silica-induced apoptosis in human alveolar macrophages — R. Iyer, A. Holian (1997)
• Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A — P. Wu, F. Hyodoh, et al. (2005)
• Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A — F. Hyodoh, A. Takata-Tomokuni, et al. (2005)
• Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell — M. Maeda, S. Yamamoto, et al. (2012)

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